Adenovirus ElB 19 kDa protein protects against cell death induced by viral infection and certain external stimuli. The Bcl-2 protein can functionally substitute for the ElB 19 kDa protein. To identify cellular targets for the 19 kDa protein, we used the two-hybrid screen in yeast. We have isolated cDNAs for three different proteins, designated Nipl, NipP, and Nip9, that interact with the 19 kDa protein. Mutational analysis indicates that these proteins do not associate with 19 kDa mutants defective in suppression of cell death, suggesting a correlation between interaction of these proteins and suppression of cell death. These proteins also associate with discrete sequence motifs in the Bcl-2 protein that are homologous to motifs of the 19 kDa protein. Our results suggest that two diverse proteins, the El B 19 kDa and the Bcl-2 proteins, promote cell survival through interaction with a common set of cellular proteins.

The 19 kDa protein coded by the adenovirus El B region confers asurvival function in adenovirus-infected cells and prevents premature cell death. Adenovirus mutants defective in the 79K gene produce large clear plaques on infected cell monolayers (Chinnadurai, 1963). Several of these mutants induce an enhanced cytopathic effect in infected cells resulting in cellular destruction (Takemori et al., 1968, 1964; Subramanian et al., 1964a) as well as fragmentation of cellular and viral DNA (Ezoe et al., 1981; Subramanian et al., 1984b; Pilder et al., 1984; White et al., 1984a; D’Halluin et al., 1985). The DNAfragmentation induced by 79K mutants is reminiscent of that observed during apoptosis (Wyllie, 1980). Although it has not yet been determined whether DNA fragmentation induced by 79K mutants occurs by an apoptotic mechanism, it is clear that the 19 kDa protein protects against a cell death program induced by viral infection, thus facilitating efficient virus replication.